Oral DAA regimens: Making HCV eradication possible in Asia
All oral direct-acting antiviral (DAA) regimens for the treatment of genotype 1 (GT1) hepatitis C virus (HCV) infection demonstrate excellent efficacy and safety in Asian patients, including the elderly and those with end-stage renal disease, according to real-world data.
“The overall cure rates and side effect profiles were excellent in real-world settings,” reports an international team of investigators who conducted a systematic review and meta-analysis of studies evaluating the efficacy of interferon (IFN)-free DAA regimens in adult patients with GT1 HCV.
Pooled data from 41 studies representing data on 8,574 patients from eight countries, including Japan, China, Hong Kong, Korea, Iran, India, Pakistan and Myanmar, showed that sustained virological response (SVR) rates for GT1 HCV were 89.9 percent (95 percent CI, 88.6–91.1; I2, 55.1 percent) with daclatasvir/asunaprevir (DCV/ASV) and 98.1 percent (97.0–99.0; I2, 41.0 percent) with ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV). [Aliment Pharmacol Ther 2018;doi:10.1111/apt.14507]
Cirrhosis status at baseline, but not prior treatment history and age, modified the effectiveness of both regimens, such that SVR rates decreased by 2.81 percent (–1.85 to 7.49) with DCV/ASV and by 2.29 percent (–0.93 to 5.60) with LDV/SOF ± RBV in the presence of cirrhosis.
Meanwhile, baseline resistance associated substitutions (RASs) severely attenuated SVR with DCV/ASV (65.4 percent vs 94.3 percent; p<0.001) and only minimally with LDV/SOF ± RBV (94.5 percent vs 99.2 percent; p=0.003).
SVR rates in patients with vs without hepatocellular carcinoma did not significantly differ with DCV/ASV (88.7 percent vs 88.0 percent; p=0.9776) but were lower with LDV/SOF ± RBV (94.1 percent vs 98.7 percent; p=0.001).
In patients with renal dysfunction, SVR with DCV/ASV was higher (93.9 percent vs 89.8 percent; p=0.046), whereas SVR with LDV/SOF ± RBV was similar (96.2 percent vs 98.2 percent; p=0.56) relative to patients with eGFR ≥50 mL/min/1.73 m2. Finally, in patients aged ≥80 years, SVR with DCV/ASV was similar (95.1 percent vs 92.0 percent; p=0.4798) as compared with patients aged <80 years.
Because the SVR rates were at least similar or higher in older patients and in those with renal dysfunction, these populations should be treated even if therapies were indicated otherwise, according to the investigators.
In terms of safety, 28.1 percent of DCV/ASV-treated patients experienced at least one adverse event (AE), with elevated alanine aminotransferase (ALT) being the most commonly reported. The pooled early discontinuation rate was 7.06 percent, and the rate of serious (S)AEs was 4.79 percent.
Among patients who received LDV/SOF ± RBV, 17.0 percent had at least one AE, but with none developing ALT elevation. The pooled early discontinuation rate was 0.82 percent, and the estimate for rate of SAEs was 1.09 percent.
Despite the presence of several limitations, the present data “have important implications for Asian countries where HCV-infected patients are ageing and can have more comorbidities such as chronic kidney disease, and these historically difficult-to-treat populations should be considered for treatment, except individuals with limited life expectancy due to nonliver-related comorbidities,” the investigators said.
“As the approval process of DAA becomes more accelerated and DAA therapy becomes more accessible to HCV-infected patients in Asia, efforts should also be targeted at early screening, diagnosis and appropriate linkage to care for at-risk patients as well as those with diagnosed infection, making HCV eradication a possibility and a reality in Asia,” they added.